1. Field of the Invention
This invention relates to a core formulation, and, more particularly, to a core formulation comprising a first layer comprising pioglitazone, which covers at least a portion of a core comprising a biguanide, metformin (i.e., glucophage), with a modulating release polymer comprising a polysaccharide, e.g. an alginate.
2. Description of the Related Art
Metformin and pioglitazone, or their salts such as the hydrochlorides, maleates, tartrates, etc., are two active ingredients of anti-diabetic drugs that are used to treat diabetic patients, e.g. human beings. These two active agents are administered orally to patients in need thereof in protocols calling for the single administration of either ingredient. Heretofore, there has not been revealed or hinted at combining both ingredients and certainly not a physically combined core formulation comprising both ingredients. The use of such a core formulation is advantageous to patients and prescribers because both medicaments are synergistic to each other in the body when used in the management of blood glucose control, i.e., diabetes. Furthermore, the use of a modulating agent, like an alginate, in the preparation, controls the rate of drug release over a clinically meaningful period to enable better control of the effect of the medicinal agents in such preparation.
This invention relates to a core formulation, and, more particularly, to a core formulation comprising a first layer comprising pioglitazone hydrochloride, which covers at least a portion of a core comprising a biguanide, one or both of which are intimately dispersed in a modulating release agent, such as a polysaccharide, e.g. an alginate.
A typical biguanide is metformin. It typically is used clinically as a pharmaceutically acceptable salt, preferably the hydrochloride salt. A commercial form of metformin hydrochloride is available as glucophage. Its chemical name is N,N-dimethylimidodicarbonimidic diamide hydrochloride. Metformin hydrochloride is a hydrochloride salt of metformin base, and as used herein, xe2x80x9cmetforminxe2x80x9d means the base compound as well as its pharmaceutically acceptable salts. Metformin is used clinically to manage non-insulin dependent diabetes mellitus or xe2x80x9cNIDDMxe2x80x9d, particularly in patients who are not effectively treated with a sulfonylurea. While it is not chemically related to the sulfonylureas, it is routinely utilized in combination with a sulfonylurea, and has been shown to be synergistic in some cases. Other biguanides such as phenformin, buformin etc. can also be used. Additionally, in the treatment of a diabetic patient the metformin, for example, and the pioglitazone hydrochloride are present in effective amounts to provide such treatment.
Metformin is an active ingredient for a commercially available drug employed to treat diabetes mellitus in a host or mammal, e.g. a human being, another animal. The typical daily effective dose for the oral treatment of a mammal, i.e., a human, ranges from about 500 mg to about 2550 mg. Typically, the dose is a single dose of about 500 mg to about 850 mg.
Pioglitazone hydrochloride, (ACTOS(copyright)), is an active ingredient for a commercially available drug employed to treat diabetes mellitus in a host, e.g. a human being. The typical daily effective dose for the oral administration to a mammal, e.g. a human being, ranges from about 15 mg to about 45 mg, given as a single dose.
Alginates are pharmaceutical excipients generally regarded as safe and used therefore to prepare a variety of pharmaceutical systems well documented in the patent literature. In this regard, reference is made to S. Bloor, U.S. Pat. No. 6,166,084; Ikeda, et al., U.S. Pat. No. 6,166,043; Ikeda, et al, U.S. Pat. No. 6,166,042; Fassler, et al, U.S. Pat. No. 6,166,004; Itakura, et al., U.S. Pat. No. 6,165,615.
A typical alginate modulating releasing agent is ammonium calcium alginate. It is typically used in injectable implants and microsphere preparations for controlled release. A commercial form of ammonium calcium alginate is Keltose, manufactured and distributed by ISP (International Specialty Products, 1361 Alps Road, Wayne, N.J. 07470). As used herein, xe2x80x9calginatexe2x80x9d means alginic acid, or any of its salts.